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Originally published In Press as doi:10.1074/jbc.M311160200 on December 29, 2003
J. Biol. Chem., Vol. 279, Issue 13, 12763-12768, March 26, 2004
The Embryotrophic Activity of Oviductal Cell-derived Complement C3b and iC3b, a Novel Function of Complement Protein in Reproduction*
Yin-Lau Lee ,
Kai-Fai Lee ,
Jia-Sen Xu ,
Qing-Yu He ,
Jen-Fu Chiu¶,
Will M. Lee||,
John M. Luk**, and
William S. B. Yeung 
From the
Department of Obstetrics and Gynaecology, Department of Chemistry, ¶Institute of Molecular Biology, ||Department of Zoology and **Department of Surgery, University of Hong Kong, Pokfulam Road, Hong Kong SAR, China
The oviduct-derived embryotrophic factor, ETF-3, enhances the development of trophectoderm and the hatching process of treated embryos. Monoclonal anti-ETF-3 antibody that abolishes the embryotrophic activity of ETF-3 recognized a 115-kDa protein from the conditioned medium of immortalized human oviductal cells. Mass spectrometry analysis showed that the protein was complement C3. Western blot analysis using an antibody against C3 confirmed the cross-reactivities between anti-C3 antibody with ETF-3 and anti-ETF-3 antibody with C3 and its derivatives, C3b and iC3b. Both derivatives, but not C3, were embryotrophic. iC3b was most efficient in enhancing the development of blastocysts with larger size and higher hatching rate, consistent with the previous reported embryotrophic activity of ETF-3. Embryos treated with iC3b contained iC3b immunoreactivity. The oviductal epithelium produced C3 as evidenced by the presence of C3 immunoreactivity and mRNA in the human oviduct and cultured oviductal cells. Cyclical changes in the expression of C3 immunoreactivity and mRNA were also found in the mouse oviduct with the highest expression at the estrus stage. Molecules involving in the conversion of C3b to iC3b and binding of iC3b were present in the human oviduct (factor I) and mouse preimplantation embryo (Crry and CR3), respectively. In conclusion, the present data showed that the oviduct produced C3/C3b, which was converted to iC3b to stimulate embryo development.
Received for publication, October 10, 2003
, and in revised form, December 16, 2003.
* This work was supported by Research Grant Council, Hong Kong, Grant HKU7319/01M (to W. S. B. Y.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
 To whom correspondence should be addressed. Tel.: 852-2855-3405; Fax: 852-2855-0947; E-mail: wsbyeung{at}hkucc.hku.hk.

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Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.
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